Our overall objective is to determine whether subjects who are heterozygotes for mutation in the gene presently identified as a cause of ataxia-telangiectasia (ATM) have a higher that expected risk of cancer, with a primary focus on breast cancer. Specific aims are the following. 1. Collaborate with investigators in Canada, Costa Rica, Germany, Israel, Italy, Poland, Turkey, and the United States of America, who have already identified ATM families, to a) obtain a reported history of cancer in patients, grandparents and aunts and uncles of A-T cases, b) verify these reported cancers, and c) determine ATM carrier status in these relatives by one of two ways: 1) if the specific ATM mutation in the proband is already known (285 of the 588 families), we will take advantage of this pre-existing information, and use a mutation specific assay such as an ASO or restriction enzyme to identify ATM heterozygotes and the specific mutation they carry; 2) if the mutation is not known, we will determine carrier status by use of haplotypes. Participating centers have collectively identified 588 A-T families to date. 2. Conduct statistical analyses to determine whether ATM heterozygotes in these families have an excess risk of cancer (greater than expected for the appropriate source population), with a primary interest in breast cancer. We anticipate that an analysis combining all known data sets will be necessary to address questions of heterogeneity in an informative manner and propose the beginnings of such an effort here. The primary analysis will include all subjects, regardless of whether their ATM status was defined by a specific mutation or by haplotypes. For the 285 families with known mutations, we will determine if there is evidence of heterogeneity by type of mutation. If there is such evidence, we will consider seeking either supplemental funds or support in a future competitive renewal to test for mutations in the remaining families. If there is not such evidence, no further testing will be done in the remaining families. We propose no new mutation screening in the current proposal. We believe this is a scientifically defensible compromise and hope that it will allow us to begin this important study.